Abstract P5-02-53: P95HER2 Expression in HER2-Positive Breast Cancer
Authors: Chih Wan Goh, Liyi Zhang, Wei-Ru Chi, Bingqiu Xiu, Jiajian Chen, Wenqing Yang, Chunxia Ao, Jianxing Tang, Jingyan Xue, Yayun Chi, Jiong Wu
Journal: Cancer Research (2023)

Abstract Background: -HER2-positive breast cancer subtype accounted for around 15-20% of all breast cancer. -The introduction of HER2-targeted therapy such as trastuzumab and pertuzumab has remarkably increased the patients’ prognosis of HER2-positive breast cancer. -However, resistance exists due to impaired drug binding to HER2 receptor and constitutive activation of HER2 downstream signaling pathways. -P95HER2 isoform is a truncated form of HER2 that retains the C terminal domain but lacks an N terminal trastuzumab binding site, leading to trastuzumab resistance in HER2-positive breast cancer. -A new P95HER2 antibody is developed to target the extracellular domain of p95HER2 in formalin-fixed paraffin-embedded (FFPE) HER2-positive breast cancer tissues by using hematoxylin and eosin (HE) staining method. Objectives: To evaluate the expression of P95HER2 and its clinicopathological characteristics in HER2-positive breast cancer. Methods: We assessed 68 HER2-positive patients (IHC 3+ or IHC 2+/in situ hybridization [ISH]+) from Fudan University Shanghai Cancer Center (FUSCC) who underwent breast cancer surgery and were treated with adjuvant chemotherapy (taxane or anthracycline or combination) plus trastuzumab from 2014 to 2016. P95HER2 HE antibody is provided by Simcere Pharma. In this study, we compared 27 patients with primary trastuzumab resistance with 41 non-relapse breast cancer patients. 14 patients have not received trastuzumab targeted therapy. P95HER2 staining of either 1+, 2+ or 3+ observed in any tumor area in HE slides was considered to be P95 HER2 positive. Chi-square test was used to determine the relationship between P95HER2 expression of patients’ characteristics. The main outcome measures were disease free-survival (DFS), distant disease-free survival (DDFS) and overall survival (OS) by using log-rank test. Univariable and multivariable Cox regression analyses were used to identify independent factors related to prognosis. Results: From 2014 to 2016, we assessed the expression of P95HER2 expression in 68 HER2 positive breast cancer patients from FUSCC. Median follow-up was 45 months. In our study, 19 (27.9%) were P95HER2 positive. P95HER2 positive expression rate is higher in premenopausal patients than in postmenopausal patients (68.4% vs 38.8%, P= 0.028). Univariable analysis showed that higher T-stage (P= 0.018), higher N-stage (P= 0.001) and P95HER2 positive expression (P= 0.033) were associated with worse DDFS. Multivariable analysis showed that higher T-stage (hazard ratio, 6.019; 95% CI, 1.205-30.078; P= 0.029) and P95HER2 positive (hazard ratio, 2.349; 95%CI, 1.03-5.358; P= 0.042) independently predicted worse DDFS. P95HER2 positive was significantly associated with shorter 5-year DDFS (42.1% vs 67.6%, P= 0.028), but has no significant difference in DFS (36.8% vs 59.5%, P= 0.072) and OS (74.8% vs 81.2%, P= 0.685). Conclusions: P95HER2 positive was found more in premenopausal patients and was associated with a higher metastasis rate, indicating that P95HER2 expression tends to be a more aggressive isoform type of HER2-positive breast cancer. P95HER2 may serve as a therapeutic target for anti-HER2 therapy. Citation Format: Chih Wan Goh, Liyi Zhang, Wei-Ru Chi, Bingqiu Xiu, Jiajian Chen, Wenqing Yang, Chunxia Ao, Jianxing Tang, Jingyan Xue, Yayun Chi, Jiong Wu. P95HER2 Expression in HER2-Positive Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-02-53.